Turner syndrome (TS) is a very common genetic disorder characterized by absence of X chromosomal material in a phenotypic female. The physical phenotypic features of TS are well-characterized, with short stature and gonadal dysgenesis being the most frequently observed. Cognitively, individuals with TS typically demonstrate normal global intellectual functioning with strengths in the verbal domain; however, many show significant deficits in visuospatial and executive functioning as well as psychosocial skills, particularly, face and emotion processing. The neural correlates of this TS cognitive-behavioral phenotype have recently begun to be explored, including neuroimaging studies of brain structure and function. However, the ability to gain meaningful insights from these studies has been limited by small sample size, large age ranges of the participants, and heterogeneity in exogenous hormone treatment status. Additionally, the impact of gene expression differences and potential epigenetic effects (i.e. X chromosome imprinting) on neural function and cognitive-behavioral outcome in TS has not yet been adequately examined. Accordingly, the primary objective of this project is to use advanced, multi-modal magnetic resonance imaging (MRI) techniques, analyses of gene expression and cognitive-behavioral assessment to elucidate the effects of X monosomy and X-linked imprinting on neurodevelopment and neural function in a large cohort of young girls with TS, pre-estrogen replacement. A multi-level, cross-disciplinary approach is proposed, capitalizing on this team of investigators' expertise in behavioral neurogenetics, cognitive neuroscience, genetics and neuroimaging, as well as on the state-of the-art infrastructure available at Stanford University School of Medicine. The overarching goal of the proposed research is to generate results with implications for the design of early and more effective interventions for girls with TS in the future. In addition, these results will have broader implications for understanding genetic and epigenetic influences on brain development and organization of neural function in humans. [unreadable] [unreadable]